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生物間代謝経路によって制御される脂質クオリティの解析

Publicly Offered Research

Project AreaQuality of lipids in biological systems
Project/Area Number 16H01369
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKeio University

Principal Investigator

長谷 耕二  慶應義塾大学, 薬学部(芝共立), 教授 (20359714)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords腸内細菌 / 脂質代謝物 / リポクオリティ / 免疫学
Outline of Annual Research Achievements

ヒトの腸管には100兆個もの細菌が共生しており、この「腸内細菌叢」は未消化物を発酵分解し、多種多様な代謝物を産生することで、外付けの臓器とも呼ぶべき代謝系を構築している。腸内代謝バランスに影響を与える因子として食事に含まれる脂質が挙げられる。とくに脂肪酸の質の違いは炎症性腸疾患の発症・再発に関わるとされているものの、これらは経験則や疫学調査に基づくものであり、その分子メカニズムについては分かっていない。申請者はこれまで、腸内細菌が栄養として摂取した中鎖・長鎖脂肪酸を代謝し、宿主が産生しえない特殊な不飽和脂肪酸代謝物に作り替える事実を見出している。興味深いことに、これら腸内代謝物には、宿主側の免疫応答を制御する活性が認められる。つまり、腸内共生系という特殊な環境において、脂質代謝物は、宿主と共生細菌のクロストークを仲介し、炎症の発症を抑制する共生因子として機能している可能性が示唆される。
本研究では、宿主と共生細菌の相互作用が織りなす「生物間代謝経路」から生じる脂質代謝物に着目し、免疫調節活性物質を探索する。さらにその作用メカニズムを解明することで、生物間代謝経路によるリポクオリティ制御の分子基盤を提供する。本研究は、これまで現象論として観察されてきた宿主―共生細菌相互作用について、脂質代謝物による免疫制御という新たな視点から分子レベルでの解明を試みるものである。具体的には、無菌マウスと通常マウスの腸内代謝物の比較解析から、免疫調節作用を担う脂質代謝物の同定を試みた。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (13 results)

All 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] Intestinal Epithelial Cell-specific Deletion of α-Mannosidase II Ameliorates Experimental Colitis2018

    • Author(s)
      Suzuki K., Yamada T, Yamazaki K, Hirota M, Ishihara N, Sakamoto M, Takahashi D, Iijima H, Hase K.
    • Journal Title

      Cell Structure and Function

      Volume: 43 Issue: 1 Pages: 25-39

    • DOI

      10.1247/csf.17022

    • NAID

      130006513071

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Macrophage extracellular chromatin release induced by Mac-1 mediated platelet-macrophage interactions triggers acute kidney injury in rhabdomyolysis.2018

    • Author(s)
      Okubo K, Kurosawa M, Kamiya M, Urano Y, Suzuki A, Yamamoto K, Hase K, Homma K, Sasaki J, Miyauchi H, Hoshino T, Hayashi M, Mayadas TN, Hirahashi J.
    • Journal Title

      Nat. Med.

      Volume: 24 Issue: 2 Pages: 232-238

    • DOI

      10.1038/nm.4462

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NALT M cells are important for immune induction for the common mucosal immune system.2017

    • Author(s)
      Date Y, Ebisawa M, Fukuda S, Shima H, Obata Y, Takahashi D, Kato T, Hanazato M, Nakato G, Williams IR, Hase K, Ohno H.
    • Journal Title

      Int. Immunol.

      Volume: 29 Issue: 10 Pages: 471-478

    • DOI

      10.1093/intimm/dxx064

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Attenuation of CD4+CD25+regulatory T cells in the tumor microenvironment by metformin, a type 2 diabetes drug2017

    • Author(s)
      Kunisada Y, Eikawa S, Tomonobu N, Domae S, Uehara T, Hori S, Furusawa Y, Hase K, Sasaki A, Udono H.
    • Journal Title

      EBioMedicine

      Volume: 25 Pages: 154-164

    • DOI

      10.1016/j.ebiom.2017.10.009

    • NAID

      120006767320

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake.2017

    • Author(s)
      Jinnohara T, Kanaya T, Hase K, Sakakibara S, Kato T, Tachibana N, Sasaki T, Hashimoto Y, Sato T, Watarai H, Kunisawa J, Shibata N, Williams I, Kiyono H, and Ohno H.
    • Journal Title

      J. Exp. Med.

      Volume: 214 Issue: 6 Pages: 1607-1618

    • DOI

      10.1084/jem.20160770

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake.2017

    • Author(s)
      Jinnohara T, Kanaya T, Hase K, Sakakibara S, Kato T, Tachibana N, Sasaki T, Hashimoto Y, Sato T, Watarai H, Kunisawa J, Shibata N, Williams I, Kiyono H, and Ohno H
    • Journal Title

      J. Exp. Med.

      Volume: in press

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice.2017

    • Author(s)
      Yang JY, Lee YS, Kim Y, Lee SH, Ryu S, Fukuda S, Hase K, Yang CS, Lim HS, Kim MS, Kim HM, Ahn SH, Kwon BE, Ko HJ, Kweon MN.
    • Journal Title

      Mucosal Immunol.

      Volume: 10 Issue: 1 Pages: 104-116

    • DOI

      10.1038/mi.2016.42

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Zinc transporter SLC39A7/ZIP7 promotes intestinal epithelial self-renewal by resolving ER stress.2016

    • Author(s)
      Ohashi, W., Kimura, S., Iwanaga, T., Furusawa, Y., Irie, T., Izumi, H., Watanabe, T., Hijikata, A., Hara, T., Ohara, O., Koseki, H., Sato, T., Robine, S., Mori, H., Hattori, Y., Watarai, H., Mishima, K., Ohno, H., Hase, K., Fukada, T.
    • Journal Title

      PLoS Genetics

      Volume: 12 Issue: 10 Pages: e1006349-e1006349

    • DOI

      10.1371/journal.pgen.1006349

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct Roles for the N- and C-terminal Regions of M-Sec in Plasma Membrane Deformation during Tunneling Nanotube Formation.2016

    • Author(s)
      Kimura S, Yamashita M, Yamakami-Kimura M, Sato Y, Yamagata A, Kobashigawa Y, Inagaki F, Amada T, Hase K, Iwanaga T, Ohno H, Fukai S.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 33548-33548

    • DOI

      10.1038/srep33548

    • NAID

      120005855947

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Microbiota-derived metabolites shape mucosal barrier and immunity2017

    • Author(s)
      Koji Hase
    • Organizer
      2017 International Congress on Obesity and Metabolic Syndromes (ICOMES)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腸内細菌定着による免疫エピゲノム修飾変化の誘導2016

    • Author(s)
      長谷耕二
    • Organizer
      大阪大学蛋白質研究所セミナー「生命システムを支配するエピジェネティクス」
    • Place of Presentation
      大阪大学蛋白質研究所(大阪・吹田)
    • Year and Date
      2016-12-22
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Microbiota-derived metabolites regulate mucosa immunity and barrier,2016

    • Author(s)
      Koji Hase
    • Organizer
      The 45th Annual Meeting of The Japanese Society for Immunology
    • Place of Presentation
      Okinawa Convention Center (Okinawa, Ginowan)
    • Year and Date
      2016-12-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Microbial metabolites facilitate IgA response in the colon2016

    • Author(s)
      Koji Hase, Yuuki Obata, Junya Isobe et al.
    • Organizer
      10th European Mucosal Immunology Group Meeting (EMIG2016)
    • Place of Presentation
      DGI Byen (Denmark, Copenhagen)
    • Year and Date
      2016-10-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-26   Modified: 2021-03-11  

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